Increase of PPARδ by dopamine mediated via DA-1 receptor-linked phospholipase C pathway in neonatal rat cardiomyocytes

Abstract

Role of peroxisome proliferator-activated receptor δ (PPARδ) in cardiac contraction has recently been established. Dopamine is one of the agents used to treat heart failure in clinics. But the mediation of PPARδ in cardiac action of dopamine is still unclear. The present study is aimed to clarify this point using neonatal rat cardiomyocytes to investigate the changes of PPARδ expression and cardiac troponin I (cTnI) phosphorylation by Western blotting analysis. Antagonists of receptors, inhibitor of phospholipase C (PLC) (U73122), calcium chelator (BAPTA-AM), and inhibitor of protein kinase A (PKAI) were also applied. We silenced PPARδ by RNAi to identify the major role of PPARδ in dopamine-induced actions. Dopamine increases PPARδ expression and cardiac troponin I (cTnI) phosphorylation in a time- and dose-dependent manner in neonatal rat cardiomyocytes. Moreover, both actions of dopamine were blocked by DA1 receptor antagonist and PLC inhibitor but not by PKAI. The increase of cTnI phosphorylation by dopamine was also inhibited in cardiomyocytes silenced by RNAi of PPARδ. We suggest that dopamine can enhance cardiac contraction mainly through an activation of DA1 receptor-linked PLC pathway to increase cellular calcium ions for the increase of PPARδ expression.